Macrophages are important mediators of resistance to infection and rejection of tumors. Bacteria or tumor cells which can induce cAMP in macrophages are able to inhibit macrophage-mediated cytotoxicity. The molecular basis of this inhibition of macrophage function is not well understood. Cyclic AMP mediated events in other cells are the result of cAMP dependent phosphorylation and subsequent modification of the function of a specific protein. The purpose of this study is to characterize cAMP dependent protein kinase activity and identify its substrate in human monocytes and macrophages. The role of this specific protein in macrophage tumor cell cytotoxicity will then be examined. Finally, experiments will determine whether cAMP mediated inhibition of macrophage function plays a role in a normal feedback mechanism for regulation of macrophage dependent immune responses. These studies will provide a greater understanding of macrophage function with clinical relevance for resistance to infections and for immunotherapy of malignant disease.